This invention relates to improved products and methods for remineralizing subsurface lesions in teeth and for mineralizing exposed tubules in dentin so as to prevent demineralization thereof. More particularly, this invention relates to liquid dentifrice products containing cationic and anionic salts having different solubilities in water and to methods of using such products to remineralize subsurface lesions and/or to mineralize exposed dentin tubules.
The primary component of the enamel and dentin in teeth is calcium phosphate in the form of calcium hydroxyapatite. While highly insoluble at normal oral pHs, the calcium phosphate in the teeth tends to be relatively soluble in acidic media. Consequently, carious lesions can form in the subsurface of a tooth when such tooth is exposed to acids formed from the glycolysis of sugars caused by various oral bacteria.
Because saliva is supersaturated with respect to calcium and phosphate ions, saliva helps protect teeth against demineralization and can slowly remineralize teeth which have become demineralized by acids. It is well known that fluoride ions can enhance the natural remineralization process and this is one of the accepted mechanisms by which fluoride toothpastes and rinses protect against caries. However, the efficacy of fluoride-containing toothpastes and rinses to remineralize teeth is limited by the modest levels of calcium and phosphate in saliva. It is evident from the prior art that it is highly desirable to increase the available concentration of calcium and phosphate ions in the oral cavity to speed up the remineralization process. However, because of calcium phosphate""s low solubility at the pH of saliva, the addition of higher levels of dissolved calcium and phosphate ions is not easily accomplished.
Remineralization of dental enamel has been carried out experimentally, both in vivo and in vitro. Some studies have concentrated on the remineralizing properties of saliva and of synthetic solutions supersaturated with respect to hydroxyapatite. Such studies comprise the subject matter of U.S. Pat. No. 3,679,360 (Rubin) and U.S. Pat. No. 4,097,935 (Jarcho).
Generally, the supersaturated solutions or slurries used in the aforementioned Rubin and Jarcho patents for remineralization experiments have been prepared from a single form of calcium phosphate. When a carious lesion is flooded with one of these supersaturated solutions, the calcium and phosphate ions in the form of precipitated hydroxyapatite remineralize the lesion. However, use of these solutions is impractical for several reasons. First, the amount of calcium and phosphate ions available for remineralization in these supersaturated solutions is too low. It is reported that it takes approximately 10,000 unit volumes of the usual supersaturated solution to produce one unit volume of mineral. Thus, remineralization by this method requires both an excessive volume of fluid and an excessive number of applications. The supersaturated solutions are inherently limited in this respect because such solutions cannot maintain their supersaturated state. When the hydroxyapatite precipitates out to the point where the solution is no longer supersaturated, new supersaturated solution must be introduced or the remineralization process stops.
Another problem with single calcium phosphate slurries is that as the hydroxyapatite precipitates out of solution, the pH of the solution changes. Unless the old solution is removed from contact with the tooth material, the solution may become too acidic or alkaline and may damage the dental tissue.
U.S. Pat. No. 4,080,440 (Digiulio et al) discloses a metastable solution of calcium and phosphate ions at a low pH (between 2.5 and 4.0) under which conditions the solubility of calcium phosphate salts is high. After penetration of the solution into demineralized enamel, remineralization results from the precipitation of calcium phosphate salts when the pH rises. Fluoride ions can be included in the metastable solution. A significant disadvantage of the use of metastable solutions is that the relatively low pH might demineralize the dental enamel and/or injure other tissue.
U.S. Pat. Nos. 4,177,258, 4,183,915 and 4,348,381 (Gaffar et al) disclose a remineralizing solution containing supersaturated concentrations of calcium ions, phosphate ions and a fluoride source stabilized by the presence of an antinucleating agent such as diamine tetramethylenephosphonic acid, ethylenediamine tetramethylenephosphonic acid and 2-phosphonobutane-tricarboxylic acid-1,2,4, or the water-soluble salts thereof. This solution is preferably adjusted to the neutral pH range where the solution is alleged to most effectively remineralize subsurface lesions. Even though the antinucleating agent would be expected to stabilize the solution, equilibrium of the supersaturated concentrations is still found difficult to maintain and avoid precipitation of hydroxyapatite and changes in the pH of the solution.
U.S. Pat. No. 4,083,955 (Grabenstetter et al) and U.S. Pat. No. 4,397,837 (Raaf et al) disclose a process for remineralizing demineralized enamel by the consecutive treatment of tooth surfaces with separate solutions containing calcium ions and phosphate ions. In this process, fluoride ions may be present in the phosphate solutions. It is immaterial which ionic solution is used to treat the teeth first. By sequentially applying calcium and phosphate ions to the tooth surface, high concentrations of the ions are able to penetrate into lesions in solution form, where the ions precipitate as a calcium phosphate salt when ions from the second treatment solution diffuse in. While apparently successful, this method involves the inconvenience of a plurality of sequential applications, which can also be time consuming.
U.S. Pat. No. 4,606,912 (Rudy et al.) teaches a method of making a clear aqueous mouthwash solution capable of remineralizing lesions in teeth by forming an aqueous solution containing a source of calcium ions and a chelating agent for calcium ions, causing the chelation of at least 50% of the calcium ions and subsequently adding a source of phosphate ions to the aqueous solution. Here too, while somewhat effective, the addition and necessary control of the amount of chelating agent makes the concept impractical.
Another problem with known remineralization techniques is that the remineralization may stop before the lesion is completely remineralized due to build-up of the remineralized tooth material in or on the outer layer of the tooth""s surface. This build-up occurs when the rate of remineralization is too fast and prevents the diffusion of the mineral into the deeper regions of the lesion, thus thwarting the full remineralization of the tooth.
U.S. Pat. Nos. 5,037,639; 5,268,167; 5,437,857; 5,427,768; and 5,460,803 (all to Tung) involve the use of amorphous calcium compounds such as amorphous calcium phosphate (ACP), amorphous calcium phosphate fluoride (ACPF) and amorphous calcium carbonate phosphate (ACCP) for use in remineralizing teeth. These amorphous compounds or solutions which form the amorphous compounds when applied either onto or into dental tissue prevent and/or repair dental weaknesses such as dental caries, exposed roots and dentin sensitivity. The compounds are claimed to have high solubilities, fast formation rates and fast conversion rates (to apatite).
Remineralization is accomplished by bringing the amorphous compound into contact with the dental tissue. This can be done directly, i.e., putting an amorphous compound directly on the tooth, or indirectly through a carrier, i.e., incorporating the amorphous compound in a carrier such as a gel, a chewing gum, or a toothpaste and applying the carrier to the dental tissue. Once contact is established with the tooth, the amorphous calcium phosphate compounds will recrystallize to the less soluble apatite form in the lesion and reform the tooth. However, under conditions where amorphous calcium phosphate compounds are stable, the quantity of calcium and phosphate released is relatively low and, therefore, remineralization is slower than desirable.
The aforementioned patents to Tung also teach the use of two-part solutions wherein a first part contains phosphate salt(s) and a second part contains calcium salt(s), wherein either the first part or the second part further contains carbonate salt(s). In addition, the Tung patents teach solutions formed by dissolving in water a solid powder containing calcium salt(s), phosphate salt(s), and carbonate salt(s). These solutions are then applied to dental tissue. The Tung patents further teach the use of non-carbonated solid powders containing mixtures of calcium salts and phosphate salts which can be applied directly to the tooth or dispersed in gel, chewing gum, or other non-aqueous mediums such as toothpaste which is placed in contact with the tooth. The patents teach that these powders are easily dissolved in saliva and then reprecipitated as an amorphous calcium phosphate compound. However, the Tung patents do not disclose the pHs of aqueous solutions formed from the non-carbonated solid powder.
Effective remineralizing/mineralizing products and methods are continually desired which do not require the presence of carbonate salts to achieve stability, remineralization and/or mineralization. It is also continually desirable to provide remineralizing/mineralizing products and methods which directly form hydroxyapatite at the subsurface of the tooth rather than first forming an amorphous calcium phosphate as an intermediate. In addition, it is continually desirable to provide a remineralization product in the form of a one-part, stable remineralizing composition which is not negatively affected by a rise in pH or temperatures or which can efficiently remineralize teeth. Finally, there is a continual need for a method of remineralizing dental enamel which employs a stable, one-part remineralizing product which does not require excessive amounts of calcium and phosphate salts or inordinately long, frequent or sequential exposure times.
Remineralizing/mineralizing one-part and two-part products which overcome many of the aforementioned problems are disclosed in copending, commonly assigned U.S. Pat. Nos. 5,603,922, 5,833,957, 5,605,675, 5,895,641, 5,645,853, 5,571,502, 5,614,175, 5,866,102, 5,817,296 and 5,858,333.
Application Ser. No. 08/512,473 discloses one-part and two-part products and methods of using same to remineralize subsurface lesions. The one-part and two-part products contain at least one water-soluble calcium salt, at least one water-soluble divalent metal salt wherein the divalent metal is other than calcium and at least one water-soluble phosphate salt. In the two-part products, the calcium and divalent metal salts are disposed in a first discrete component, and the phosphate salt(s) is disposed in a second discrete component. The two-part product may further contain a dispensing means for allowing the first and second components to be simultaneously dispensed from the product so as to permit the dispensed first and second components to simultaneously contact the tooth or teeth being treated. The aqueous solution formed by mixing the salts used in the one-part and two-part products has a pH of from about 4.0 to about 7.0.
U.S. Pat. Nos. 5,605,675 and 5,895,641 discloses a two-part product and method of using same for remineralizing dental enamel, wherein the product contains a first discrete component containing at least one water-soluble calcium salt and a second discrete component containing at least one water-soluble phosphate salt and at least one water-soluble fluoride salt. The product may further contain a means for allowing the first and second components to be simultaneously dispensed from the product. The first and second components of the product each have a pH such that when the two components are mixed to form an aqueous mixed solution, the solution has a pH of from about 4.5 and 10.0.
U.S. Pat. No. 5,645,853 is directed to a chewing gum product and method of using same for remineralizing subsurface lesions in teeth, wherein the product contains a water-soluble cationic portion composed of at least one water-soluble calcium salt and at least one water-soluble, non-toxic divalent metal salt wherein the divalent metal is other than calcium; a water-soluble anionic portion containing at least one water-soluble phosphate salt; and a gum base. The anionic and cationic portions are disposed in the product such that chewing of the product in the presence of water and/or saliva causes the anionic and cationic portions to be simultaneously released into the water and/or saliva so as to form a mixed aqueous solution therewith. The anionic and cationic portions each have a pH when dissolved in water and/or saliva such that the mixed aqueous solution has a pH of from about 4.0 to 7.0.
U.S. Pat. Nos. 5,571,502, 5,614,175 and 5,866,102 are directed to one-part, non-aqueous products and methods of using same for remineralizing subsurface lesions, wherein the products contain at least one water-soluble calcium salt; at least one water-soluble phosphate salt; either a stabilizer or a hydrophilic, non-aqueous, water-soluble vehicle; and, optionally, at least one water-soluble fluoride salt. When the components are mixed with water or saliva to form an aqueous mixed solution, the solution has a pH of from about 4.5 to about 10.0.
In the one-part and two-part products disclosed in the foregoing applications, the cationic and anionic components are kept separate from one another until use of the product. In addition, the cations and anions are delivered simultaneously to the surface of the tooth being treated. These factors, along with the pH of the aqueous solution and the use in some cases of at least one water-soluble divalent metal salt, are helpful to allowing the cations and anions to have ample time to diffuse through the surface of the tooth to the subsurface before undergoing precipitation.
For mineralization or remineralization of enamel or dentin to occur, the concentration of calcium and phosphate ions in saliva must be above the concentration required to saturate the solution with respect to the formation of calcium hydroxyapatite, octacalcium phosphate, dicalcium phosphate dihydrate, or other form of insoluble calcium phosphate. At pHs above about 6.5, these requirements are met by the levels of calcium and phosphate in normal human saliva. However, because the concentration of calcium and phosphate ions in normal human saliva is only modest, even at pHs above 6.5, the rate of mineralization produced by normal saliva is very slow even when fluoride is present to catalyze the process. When the pH is above about 7, raising the concentration of calcium and phosphate ions much beyond that normally present in saliva does not, however, significantly increase remineralization. Because of the high insolubility of calcium phosphate salts above pHs of about 7, excessively rapid precipitation occurs which does not allow time for the ions to penetrate the tooth.
At pHs below about 7, significant remineralization will occur only if the concentration of calcium and phosphate ions in the saliva is above the concentration required to saturate the solution with respect to the formation of dicalcium phosphate dihydrate. Under these pH conditions, it has been demonstrated that remineralization can be accelerated by increasing the degree of supersaturation in saliva. Inasmuch as the solubility of dicalcium phosphate increases with decreasing pH, it has been found that when lesions are remineralized with solutions having a pH in the range of 4.5 to 7.0 and containing supersaturated quantities of calcium and phosphate ions, the optimum concentration of calcium ions needed to maximize the process increases with decreasing pH. Below a pH of about 4.0, dicalcium phosphate dihydrate becomes the stable precipitating species from supersaturated solutions. Under these pH conditions, it takes very high levels of calcium and phosphate to saturate the solutions. Under such conditions, there is a real danger with fairly high concentrations of calcium and phosphate hat the solution will be undersaturated and demineralization of the teeth being treated will occur.
It has also been found that the simultaneous provision of very high calcium and phosphate ion concentrations can result in premature precipitation of the calcium salt before the ions can penetrate the tooth or premature precipitation so as to block the entrances of the pores in tooth enamel and dentin and thereby prevent further remineralization.
Thus, a problem apparently exists in that to control untimely precipitation, the concentration of either the dissolved calcium ions or the dissolved phosphate ions needs to be limited. This in turn would be expected to disadvantageously limit the maximum rate of mineralization or remineralization which could be accomplished.
In addition, the use of very high calcium and fluoride ion concentrations can result in premature precipitation of the fluoride ions before these ions can penetrate the tooth. As mentioned previously herein, fluoride ions can enhance the natural remineralization process. However, sufficient levels of fluoride ions are generally required to be present. Calcium cations and fluoride anions precipitate to form calcium fluoride, a salt which is sparingly soluble in water. The formation of calcium fluoride is undesirable since it reduces the amount of free fluoride anions available for use in the remineralization process. Thus, it is desirable to provide a remineralizing product wherein the solution used to treat the teeth contains sufficient levels of dissolved fluoride anions to enhance the remineralization of the subsurface lesions.
Although the remineralization products disclosed in the aforementioned copending, commonly assigned patent applications are stable, it is continually desirable to provide alternative products which minimize the risk of premature precipitation of the cations and anions, particularly of the fluoride anions.
Accordingly, it is a primary object of this invention to provide products and methods for the remineralization and the prevention of demineralization of human teeth, wherein the products and methods are capable of effectively incorporating calcium ions, phosphate ions and fluoride ions into the subsurface of a tooth.
It is a further object of this invention to provide products and methods for the remineralization and the prevention of demineralization of human teeth, wherein the precipitation of the calcium, phosphate and fluoride ions is substantially avoided prior to diffusion of the ions into the subsurface of the tooth without reducing the rate of remineralization at the subsurface of the tooth.
It is another object of this invention to provide products and methods for the remineralization and the prevention of demineralization of human teeth, which do not require excessive amounts of solution or inordinately long or frequent exposure times.
It is still another object of the present invention to provide products for the remineralization and the prevention of demineralization of human teeth, wherein the products are easily usable by the consumer and do not differ significantly, in flavor or appearance, from customary dental cosmetics.
It is yet another object of this invention to provide an improved product and a method of preparing such product, wherein the product is maintainable in a single container, substrate or matrix and is capable of remineralizing lesions in the teeth and mineralizing normal teeth to prevent cariogenic lesions from forming therein.
It is a further object of this invention to provide remineralizing/mineralizing products and methods which can directly form hydroxyapatite in the subsurface of a tooth subsurface without first forming an amorphous calcium phosphate as an intermediate.
It is another object of this invention to provide two-part remineralizing/mineralizing products and methods of using same, wherein the products contain calcium salt(s) in a first part and phosphate salt(s) in a second part separate from the first part prior to introduction of the product into the oral cavity but wherein the product will simultaneously dispense the first and second parts from the product for use in the oral cavity.
Yet another object of the present invention is to provide products having the characteristics set forth in the foregoing objects and which are in the form of a toothpaste, gel, professional gel, cream, mouthwash, mouth rinse, and the like.
A further object of the present invention is to provide remineralization/mineralization methods using products having the characteristics set forth in the preceding objects.
It is yet another object of the present invention to provide an improved product and method having the characteristics set forth in the preceding objects wherein the active ingredient in the product is fluoride.
These and other objects which are achieved according to the present invention can be readily discerned from the following description.
The present invention provides effective remineralizing/mineralizing liquid products and methods of using same which overcome the aforementioned problems and achieve the foregoing objects.
Specifically, the present invention provides liquid products for remineralizing subsurface lesions and/or for mineralizing exposed dentin tubules in teeth, containing:
(a) a cationic component containing at least one partially water-soluble calcium salt;
(b) an anionic component containing at least one water-soluble phosphate salt and at least one water-soluble fluoride salt; and
(c) a separating means disposed to separate components (a) and (b),
wherein components (a) and (b) have a pH in water such that a mixed aqueous composition formed by mixing components (a) and (b) with water and/or saliva has a pH of from about 4.0 to about 10.0;
further wherein the product contains an amount of the calcium salt such that in the mixed aqueous composition a first portion of the calcium salt exists as dissolved calcium cations and a second portion of the calcium salt exists as undissolved calcium salt, the aqueous composition further containing phosphate anions released by the phosphate salt and fluoride anions released by the fluoride salt.
In the present invention, when the mixed aqueous composition is applied to a tooth (or teeth), the calcium cations and the phosphate and fluoride anions in the aqueous composition do not immediately precipitate but rather first diffuse through the surface of the tooth to the subsurface and/or dentin thereof, where the ions then combine to form an insoluble precipitate on the demineralized subsurface lesion(s) and/or on the exposed dentin tubule(s).
This invention is based on the discovery that such delayed precipitation of the calcium cations and the phosphate and fluoride anions until such ions have diffused through the tooth surface to the subsurface and/or dentin can be achieved by using in the cationic component at least one calcium salt having partial water-solubility at a pH of from about 4.0 to about 10.0. With the use of the partially water-soluble calcium salt(s) in the cationic component of the products of this invention, the calcium cations and the phosphate and fluoride anions in the mixed aqueous composition used to treat the tooth are able to remain soluble for the period of time sufficient to allow the cations and anions to diffuse through the surface of the tooth to the subsurface and/or dentin thereof, where, as stated above, the ions react to form an insoluble precipitate on the demineralized lesion(s) and/or exposed tubule(s).
This invention is also based on the discovery that the use of at least one partially water-soluble calcium salt in the products of this invention allows a greater level of free fluoride anions to be available for absorption by the tooth being treated than would be available when water-soluble calcium salts are used instead.
Thus, an important advantage of using the partially water-soluble calcium salt(s) in the present invention is that at any point in time the low concentration of calcium cations does not insolubilize either the phosphate anions or the fluoride anions, the cations and anions both being used in the remineralization and/or mineralization process.
Another advantage resulting from the use of the partially water-soluble calcium salt(s) in the present invention is that high concentrations of the undissolved calcium salt can be added to the dentifrice formulation without the danger of excessive concentrations of calcium cations being released at any one time to the saliva.
A further advantage resulting from the use of the partially water-soluble calcium salt(s) in the present invention is that, as the calcium cations in the mixed aqueous composition are used up (i.e., precipitated), the undissolved calcium salt can release additional calcium cations to the composition so as to maintain the rate of the remineralization and/or mineralization process.
Another particularly important advantage of using the partially water-soluble calcium salt(s) in the present invention is that, in the aqueous composition used to treat the teeth, the calcium salt(s) releases an amount of calcium cations sufficient to promote remineralization but insufficient to precipitate the fluoride. Thus, the maximum level of fluoride anions remains available for absorption by the tooth during application of the composition thereto.
Thus, the use of the partially water-soluble calcium salt(s) in the present invention provides a practical way to ensure close to optimum levels of calcium cations throughout the remineralization and/or mineralization process.
As stated hereinabove, the products of this invention remineralize and/or mineralize teeth using combinations of partially water-soluble calcium salts, water-soluble phosphate salts and fluoridating agents. Fluoride itself is a known remineralizing agent. The provision of calcium and phosphate salts in this invention serves to enhance the efficacy of the fluoride. Because of the short periods of exposure during brushing with toothpastes or rinsing with mouth rinses, it is believed that significant remineralization will not occur with these products in the absence of an active fluoride.
The products of the present invention provide substantially improved remineralization and mineralization as compared with the prior art products discussed hereinabove.
In addition, the methods of the present invention overcome the disadvantages of the prior art methods discussed hereinabove in that the methods of this invention effect subsurface remineralization rather than surface remineralization. Since dental caries begins as a subsurface demineralization of the dental enamel, subsurface remineralization arrests and repairs the carious lesion before any permanent structural damage to the tooth occurs.
Furthermore, the methods of the present invention do not require preparation of the enamel surface, capping of the tooth, or removal of decay products.
In addition, consumers may conveniently practice the methods of the present invention without substantially changing their dental care habits.
As stated hereinabove, the present invention provides liquid products and methods of using same to remineralize subsurface lesions and/or mineralize exposed dentin tubules in teeth.
As used herein, the term xe2x80x9cliquidxe2x80x9d refers to a material having a consistency like that of a solution, a concentrate, a paste, a gel, a cream or the like.
The products of this invention are composed of a cationic component, an anionic component, and a separating means for separating the cationic and anionic components. The cationic component contains at least one partially water-soluble calcium salt and preferably at least one non-toxic, water-soluble salt of a divalent metal other than calcium. The anionic component contains at least one water-soluble phosphate salt, and at least one water-soluble fluoride salt. The separating means may be in the form of a liquid medium in which the anionic and cationic components are insoluble or in the form of a physical barrier. As used herein, the term xe2x80x9cpartially water-solublexe2x80x9d with respect to the calcium salt component means that the solubility of the salt is greater than that of dicalcium phosphate dihydrate in an aqueous solution having a pH of about 7.0 and a temperature of about 25xc2x0 C. but wherein less than 0.25 gram of the calcium salt will dissolve in 100 ml of water at a temperature of 20xc2x0 C. In an aqueous solution having a pH of about 7.0 at a temperature of about 25xc2x0 C., dicalcium phosphate dihydrate generally releases about 40 ppm of calcium cations. Thus, the calcium salt used in the present invention generally has a minimum solubility such that the salt is capable of releasing more than about 40 ppm of calcium cations in an aqueous solution having a pH of about 7.0 at a temperature of about 25xc2x0 C. Preferably, the calcium salt(s) used in this invention has a solubility in such aqueous solution such that the salt(s) releases from about 100 ppm to no more than about 1400 ppm of calcium cations.
The term xe2x80x9cwater-solublexe2x80x9d as used herein with respect to the phosphate, fluoride and divalent metal salts suitable for use in the present invention means that at least 0.25 gram of the salt will dissolve in 100 ml of water at a temperature of about 20xc2x0 C.
In preferred embodiments, the products of this invention contain water, a concentration of dissolved calcium cations released by the calcium salt released in the water, and a concentration of an undissolved form of such calcium salt. Preferably, the cationic and anionic components of the products of this invention are both aqueous, wherein the cationic component contains no more than about 0.14%, more preferably no more than about 0.08%, most preferably from about 0.01% to about 0.05%, by weight of dissolved calcium cations released by the calcium salt, and at least about 0.05%, more preferably at least about 0.20%, most preferably from about 0.20% to about 0.30%, by weight of the undissolved form of the calcium salt.
The products of this invention may be in the form of one-part products or in the form of two-part products. Preferably, the products of this invention are in the form of two-part products.
One-part products of this invention contain the cationic and anionic components suspended in a non-aqueous, hydrophilic liquid carrier medium which acts as the separating means. Upon mixing of the one-part product with water and/or saliva, the liquid carrier medium releases the cationic and anionic components into the water and/or saliva so as to form the mixed aqueous composition. In preferred embodiments, the liquid carrier medium simultaneously releases the anionic and cationic components into the water and/or saliva.
The two-part products of this invention contain first and second discrete parts, wherein the first discrete part contains the cationic component and the second discrete part contains the anionic component. The separating means separates the first and second discrete parts from one another. In the two-part products of this invention, the anionic and cationic components are both in liquid form. The anionic and cationic components may both be aqueous or non-aqueous, or one component may be aqueous while the other component is non-aqueous. As stated previously herein, in preferred embodiments of the products of this invention, both the anionic and the cationic components are aqueous.
If the cationic and anionic components are both aqueous in the two-part products, the separating means is a physical barrier separating the first and second discrete parts from one another. If one or both of the cationic and anionic components are non-aqueous, the separating means can be a solid physical barrier or a non-solid barrier formed by the mutual insolubility of the cationic and anionic components. The two-part products of this invention further contain a dispensing means for dispensing the anionic and cationic components from the products. In preferred embodiments, the dispensing means is capable of simultaneously dispensing the anionic and cationic components from the product. When a product within the scope of this invention is ready to be used, the cationic and anionic components are mixed together with water and/or saliva to form the mixed aqueous composition previously mentioned herein. The anionic and cationic components are mixed only when the components are introduced into the oral cavity or immediately before their introduction into the oral cavity.
The cationic and anionic components of the products of this invention must each have a pH in water such that the mixed aqueous composition has a pH of from about 4.0 to about 10.0, preferably from greater than about 4.0 to about 7.0, more preferably from about 4.5 to about 6.5, and most preferably from about 5.00 to about 5.75.
The partially water-soluble calcium salt(s) is present in the products of this invention in an amount such that in the mixed aqueous composition a first portion of the calcium salt(s) is present as dissolved calcium cations and a second portion of the calcium salt(s) is present as undissolved calcium salt. Preferably, the mixed aqueous composition will contain from about 100 ppm to no more than about 1400 ppm, more preferably from about 100 ppm to no more than about 800 ppm, most preferably from about 100 ppm to about 500 ppm, of the dissolved calcium cations. In addition, the mixed aqueous composition will preferably contain at least about 500 ppm, more preferably at least about 2000 ppm, most preferably from about 2000 ppm to about 3000 ppm, of the undissolved calcium salt.
If the product is a two-part product and the cationic component therein is aqueous, such aqueous cationic component will also contain dissolved calcium cations and undissolved calcium salt. The amount of dissolved calcium cations in the aqueous cationic component is preferably no more than about 0.14%, more preferably no more than about 0.08%, most preferably from about 0.01% about 0.05%, by weight of the cationic component. In addition, the amount of undissolved calcium salt in the aqueous cationic component is preferably at least about 0.05%, more preferably at least about 0.20% and most preferably from about 0.20% to about 0.30%, by weight of the cationic component.
The phosphate and fluoride salts are respectively present in the products of this invention in amounts such that the mixed aqueous composition will further contain dissolved phosphate anions and dissolved fluoride anions. In two-part products of this invention wherein the anionic component is aqueous, such aqueous anionic component will also contain dissolved phosphate anions and dissolved fluoride anions.
The mixed aqueous composition will preferably contain at least about 100 ppm, more preferably from about 500 ppm to about 40,000 ppm, of the phosphate anions; and preferably from about 100 ppm to about 5000 ppm, more preferably from about 850 ppm to about 2000 ppm, of the fluoride anions.
As stated hereinabove, the products of this invention further contain at least one non-toxic, water-soluble salt of a divalent metal other than calcium. If used, the divalent metal salt(s) releases divalent metal cations which help to stabilize the mixed aqueous composition against rapid precipitation of the calcium cations and the phosphate and fluoride anions. The remineralizing cations and anions can then diffuse through the tooth surface to the demineralized subsurface lesion(s) and/or the exposed dentin tubule with a reduced risk of forming a precipitate bound to the tooth surface. As a result, when an effective amount of the divalent metal cations is used, the subsurface lesion is more effectively remineralized or desensitized and/or the exposed dentin tubule is more effectively mineralized.
When used, the divalent metal salt(s) is preferably present in the products of this invention in an amount such that the mixed aqueous composition will contain at least about about 100 ppm, more preferably from about 500 ppm to about 40,000 ppm, of the divalent metal cations released by the divalent metal salt(s).
The products of this invention preferably contain from about 0.05% to about 15.0% by weight, more preferably from about 0.10% to about 10.0% by weight, of the calcium salt(s); from about 0.05% to about 15.0% by weight, more preferably from about 0.10% to about 10.0% by weight, of the phosphate salt(s); and from about 0.01% to about 5.0%, more preferably from about 0.02% to about 2.0%, by weight of the fluoride salt(s). In preferred embodiments, the products of this invention further contain at least 0.001%, preferably from about 0.0001% to about 2.0%, and more preferably from about 0.01% to about 1.0%, by weight of the divalent metal salt(s) discussed previously herein.
The products of this invention contain a molar ratio of the calcium salt(s) to the phosphate salt(s) of preferably from about 0.01:1 to about 100:1. Most preferably, the concentration of the calcium salt(s) and the concentration of the phosphate salt(s) are preferably essentially the same in the products of this invention. The concentration of the calcium salt(s) always exceeds the solubility of such salt, whereas the concentration of the phosphate salt(s) may be as high or even higher than the solubility thereof.
Non-limiting examples of calcium salts of partial water-solubility suitable for use in this invention include calcium sulfate, anhydrous calcium sulfate, calcium sulfate hemihydrate, calcium sulfate dihydrate, calcium dl-malate trihydrate , calcium tartrate, calcium malonate, calcium succinate, and mixtures of the foregoing. Calcium sulfate is preferred.
The partially water-soluble calcium salt component of the products of this invention can be prepared in situ, for example, by preparing mixtures of an acid such as, e.g., tartaric acid, and a water-soluble calcium salt such as, e.g., calcium nitrate, and adjusting the pH as needed.
In the present invention, the principle known as the xe2x80x9ccommon ion effectxe2x80x9d can be used to control the solubility of the partially water-soluble calcium salt used in the present invention and to optimize calcium release and fluoride stability. To achieve the common ion effect, a salt can be added to the product or solution of this invention wherein the anion of the salt is the same as the anion present in the calcium salt used in the particular product or solution. In the present invention, the sodium, potassium and ammonium salts are preferred for use to achieve the common ion effect. However, an anion which is part of another functional ingredient may also be added. For example, the use of magnesium sulfate in a calcium sulfate-based formulation would supply at least some of the needed sulfate anion.
Suitable water-soluble inorganic phosphate salts for use in the present invention include, for example, alkali salts and ammonium salts of orthophosphoric acid, such as, e.g., potassium, sodium or ammonium orthophosphate; monopotassium phosphate; dipotassium phosphate; tripotassium phosphate; monosodium phosphate; disodium phosphate and trisodium phosphate.
Suitable fluoride salts for use in the present invention include the alkali fluorides such as sodium, potassium, lithium or ammonium fluoride; tin fluoride; indium fluoride; zirconium fluoride; copper fluoride; nickel fluoride; palladium fluoride; fluorozirconates such as sodium, potassium or ammonium fluorozirconate or tin fluorozirconate; fluorosilicates; fluoroborates; and fluorostannites.
Organic fluorides, such as the known amine fluorides, are also suitable for use in the products of the present invention.
Water-soluble alkali metal monofluoro-phosphates such as sodium monofluorophosphate, lithium monofluorophosphate and potassium monofluorophosphate, (the sodium monofluorophosphate being preferred) may be employed. In addition, other water-soluble monofluorophosphate salts may be employed, including, for example, ammonium monofluorophosphate, aluminum monofluorophosphate, and the like. If monofluorophosphate salts are used as the fluoride source in two-phase systems, these salts could be present in the first phase along with the calcium cations without departing from the present invention. However, this is less desirable due to the potential loss of fluoride as a result of the formation of sparingly soluble calcium fluoride.
The divalent metal salt(s) which can be used in the products of the present invention may be any water-soluble, non-toxic divalent metal compound which will stabilize the calcium, phosphate and fluoride ions so that these ions do not rapidly or prematurely precipitate before diffusing into the teeth. In practice, however, it has been found that at least one member selected from the group consisting of magnesium, strontium, tin, and zinc, with magnesium being preferred, is the most effective divalent metal in stabilizing the system.
Suitable magnesium compounds include, for example, magnesium acetate, magnesium ammonium sulfate, magnesium benzoate, magnesium bromide, magnesium borate, magnesium citrate, magnesium chloride, magnesium gluconate, magnesium glycerophosphate, magnesium hydroxide, magnesium iodide, magnesium oxide, magnesium propionate, magnesium D-lactate, magnesium DL-lactate, magnesium orthophosphate, magnesium phenolsulfonate, magnesium pyrophosphate, magnesium sulfate, magnesium nitrate, and magnesium tartrate. Preferred magnesium compounds are magnesium chloride, magnesium acetate and magnesium oxide.
Suitable strontium compounds include, for example, strontium acetate, strontium ammonium sulfate, strontium benzoate, strontium bromide, strontium borate, strontium caprylate, strontium carbonate, strontium citrate, strontium chloride, strontium gluconate, strontium glycerophosphate, strontium hydroxide, strontium iodide, strontium oxide, strontium propionate, strontium D-lactate, strontium DL-lactate, strontium pyrophosphate, strontium sulfate, strontium nitrate, and strontium tartrate. Preferred strontium compounds are strontium acetate, strontium chloride, strontium nitrate.
Suitable tin compounds include, for example, stannous acetate, stannous ammonium sulfate, stannous benzoate, stannous bromide, stannous borate, stannous carbonate, stannous citrate, stannous chloride, stannous gluconate, stannous glycerophosphate, stannous hydroxide, stannous iodide, stannous oxide, stannous propionate, stannous D-lactate, stannous DL-lactate, stannous orthophosphate, stannous pyrophosphate, stannous sulfate, stannous nitrate, and stannous tartrate. A preferred tin compound is stannous chloride.
Suitable zinc compounds include, for example, zinc acetate, zinc ammonium sulfate, zinc benzoate, zinc bromide, zinc borate, zinc citrate, zinc chloride, zinc gluconate, zinc glycerophosphate, zinc hydroxide, zinc iodide, zinc oxide, zinc propionate, zinc D-lactate, zinc DL-lactate, zinc pyrophosphate, zinc sulfate, zinc nitrate, and zinc tartrate. Preferred zinc compounds are zinc acetate, zinc chloride, zinc sulfate, and zinc nitrate.
As stated previously herein, the separating means used in the one-part products of this invention is preferably a non-aqueous, hydrophilic liquid carrier medium, the term xe2x80x9cliquidxe2x80x9d being defined as set forth previously herein. Such non-aqueous liquid carrier mediums include any carrier medium which is conventionally used in such dental products as toothpastes, gels, creams, mouthwashes and rinses. Examples of suitable non-aqueous carrier mediums include non-aqueous solvents such as, e.g., ethyl alcohol, glycerine and propylene glycol. Preferably, the non-aqueous, hydrophilic liquid carrier medium is a polyethylene oxide having a molecular weight of about 400 (also known under the designation xe2x80x9cCarbowax 400xe2x80x9d).
As stated previously herein, in the two-part products of this invention, the anionic and cationic components may both be aqueous or non-aqueous, or one component may be aqueous and the other component non-aqueous.
In the two-part products of this invention, if one or both of the cationic and anionic components are aqueous, the mixed aqueous composition can be formed by dispensing the cationic and anionic components from the product and simply mixing the two components together. If neither component is aqueous, the mixed aqueous composition can be formed by mixing the two dispensed components with saliva and/or water in the mouth or with water provided from an external source.
While completely aqueous compositions are preferred in the present invention for application to the teeth, non-aqueous solvents may be employed in combination with water and/or saliva to form an aqueous/non-aqueous medium. Suitable non-aqueous solvents include, e.g., ethyl alcohol, glycerine and propylene glycol. Solvent systems suitable for use in the present invention are those which are safe for use in the mouth.
As stated previously herein, the mixed aqueous composition formed by mixing the cationic and anionic components with water and/or saliva has a pH of from about 4.0 to about 10.0, preferably from greater than about 4.0 to about 7.0, more preferably from about 4.5 to about 6.5, and most preferably from about 5.0 to about 5.75. At a pH within such range, enough of the calcium cations, phosphate anions and fluoride anions remain soluble for the period of time required to remineralize the subsurface lesions and/or mineralize the exposed tubules of the dental enamel. If the mixed aqueous composition has a pH below about 3, demineralization will occur rapidly. A pH below about 2.5 is undesirable from a safety standpoint.
The pH of the mixed aqueous composition may be adjusted to the desired pH by methods well known in the art. The pH may be lowered by the addition of any acid which is safe for use in the oral cavity and which yields the desired pH at the amount employed. Examples of suitable acids include acetic acid, phosphoric acid, citric acid and malic acid.
The mixed aqueous composition and the insoluble precipitate formed therefrom in the present invention must both have acceptable levels of toxicity (i.e., the particular ions, in the amounts used in the remineralization/mineralization process, must be non-toxic) and must both be otherwise compatible in the oral environment.
The present invention further provides methods of remineralizing one or more lesions formed in a subsurface of at least one tooth and/or one or more exposed tubules in a dentin portion of at least one tooth. Broadly, the methods of this invention involve the steps of:
(1) providing the previously-described mixed aqueous composition; and
(2) applying the mixed aqueous composition to the tooth for a period of time sufficient to allow diffusion of the calcium cations, the phosphate anions and the fluoride anions through a surface of the tooth to the subsurface and/or to the dentin portion, wherein the cations and anions precipitate at the subsurface to form an insoluble salt on the lesion(s) so as to remineralize the lesion(s), and/or precipitate at the dentin portion to form an insoluble salt on the exposed tubule(s) so as to mineralize the exposed tubule(s).
The mixed aqueous composition is applied to the tooth for preferably at least about 10 seconds, more preferably at least about 30 seconds, and most preferably at least about 1 minute. The delayed precipitation of the anions and cations for a time period sufficient to permit the ions to diffuse to the dentin and/or subsurface lesion is a benefit accruing at least in part from the use in this invention of the partially water-soluble calcium salt(s). The presence of the divalent metal salt(s) further promotes such delayed precipitation.
The pH of the mixed aqueous composition remains relatively constant after its introduction into or initial formation in the oral cavity. Under some conditions, calcium fluoride phosphate readily precipitates at this pH, but most surprisingly, while some precipitation may occur immediately and to a small extent even before application to the teeth, substantially greater amounts of calcium, phosphate and fluoride ions remain in solution to diffuse into the teeth and remineralize the demineralized dental enamel. As stated hereinabove, this delayed precipitation is due at least in part to the use of the partially water-soluble calcium salt(s) in the present invention, with the divalent metal salt(s) also playing an important role.
In general, the partially water-soluble calcium salt(s) is such that the amount of dissolved calcium cations in the mixed aqueous composition is such that the concentration of dissolved fluoride anions in the mixed aqueous composition is equal to at least 75% by weight of fluoride anions in the fluoride salt in the product for a period of up to about 1 minute after formation of the mixed aqueous composition.
When the aqueous anionic component is aqueous and contains the fluoride salt(s) as dissolved fluoride anions, it has been found that the mixed aqueous composition of the present invention has a concentration of fluoride anions equal to about at least about 75% of the concentration of fluoride anions in the aqueous anionic component for a period of up to about 1 minute after formation of the mixed aqueous composition. In other words, at least about 75% by weight of the fluoride anions in the anionic aqueous component remains available for absorption in the mixed aqueous composition. This is an important benefit provided by the products and methods of this invention.
Therefore, the use of partially water-soluble calcium salt(s) in the products of this present invention allows a higher level of free fluoride anions to be present in the mixed aqueous composition and thus available for absorption.
As stated previously herein, the use of the partially water-soluble calcium salt(s) in this invention also provides a benefit in that as the calcium cations in the mixed aqueous composition are precipitated, the undissolved calcium salt releases additional calcium cations to the composition so as to maintain the rate of the remineralization and/or mineralization process.
When using the two-part aqueous products of this invention, the time period between the mixing of the first and second parts and the application of the resulting mixed aqueous composition to the teeth should not exceed 1 minute, and preferably is less than 1 minute. With a toothpaste, gel, and the like, mixing is achieved on the surface to the teeth while brushing. An important feature of the present invention lies in the mixing of the anionic and cationic components and the quick and timely application of the resulting mixed composition to the tooth so that the ions will diffuse through the surface of the tooth to the dentin and/or subsurface of the tooth, where the ions will precipitate calcium phosphate, calcium fluoride, and calcium fluoroapatite in the dentin and/or subsurface enamel of the teeth. However, before such precipitation occurs, the mixed aqueous composition must quickly be applied to the teeth.
The remineralizing-mineralizing precipitate formed in the present invention is a calcium phosphate or a hydroxyapatite (the natural constituent of tooth enamel) with incorporated fluoride ions. Because of the presence of the fluoride ions in the mixed aqueous composition used in this invention, the remineralized enamel is more resistant to demineralization than was the original enamel. Therefore, use of the mixed aqueous composition in accordance with the present invention not only remineralizes the enamel but also renders such enamel more resistant to subsequent demineralization than was the original enamel.
In preferred embodiments, the products of this invention are in the form of toothpastes, gels, professional gels, creams, mouthwashes or mouthrinses. More preferably, the products of this invention are in the form of two-part aqueous products, wherein the anionic and cationic components are both aqueous.
A two-part aqueous product within the scope of this invention can be prepared as follows. At least one calcium salt of partial water-solubility in a concentration of from about 0.05% to about 15.0% by weight is mixed in an aqueous medium to form a cationic aqueous composition containing calcium cations and undissolved calcium salt. At least one water-soluble divalent metal salt other than a calcium salt can be added to the cationic aqueous composition at a concentration of greater than about 0.001% by weight and preferably from about 0.001% to about 2.0% by weight. At least one water-soluble phosphate salt at a concentration of from about 0.05% to about 15.0% by weight is dissolved in an aqueous medium to form an anionic aqueous composition. At least one water-soluble fluoride salt is added to the anionic aqueous composition at a concentration of from about 0.01% to about 5.0% by weight. The pH of each composition is adjusted so that, upon mixing, the pH of the final mixed aqueous composition will range from about 4.0 to about 10.0. The two aqueous compositions are then mixed to produce a stable supersaturated or nearly supersaturated aqueous composition of calcium fluoride phosphate containing excess undissolved calcium salt.
In addition to the active anionic and cationic salts previously described herein, toothpaste, gel and cream products within the scope of this invention preferably further contain from about 0.5% to about 65%, preferably from about 5% to about 40%, by weight of an abrasive; from about 0.2% to about 5% by weight of a sudsing agent; from about 0.1% to about 5% by weight of a binding agent; from 0% to about 50% by weight of a humectant; and the balance, water and minors. From about 1.0% to about 10.0% by weight of an inorganic thickener such as hydrated silica may also be added.
Suitable abrasives which can be used in the present invention include, for example, silica xerogels. Other conventional toothpaste abrasives can be used in the products of this invention, such as, e.g., beta-phase calcium pyrophosphate, dicalcium phosphate dihydrate, anhydrous calcium phosphate, calcium carbonate, zirconium silicate, and thermosetting polymerized resins. Silica aerogels and insoluble metaphosphates such as insoluble sodium metaphosphate can also be used. Mixtures of abrasives can be also be used. Silica xerogel abrasives are preferred.
Suitable sudsing agents for use in the present invention include those which are reasonably stable and which form suds throughout the period of application. Preferably, non-soap anionic or nonionic organic synthetic detergents are employed. Examples of such agents include, e.g., water-soluble salts of alkyl sulfate having from 10 to 18 carbon atoms in the alkyl radical, such as sodium lauryl sulfate; water-soluble salts of sulfonated monoglycerides of fatty acids having from 10 to 18 carbon atoms, such as sodium monoglyceride sulfonate; salts of C10-C18 fatty acid amides of taurine, such as sodium N-methyl taurate; salts of C10-C18 fatty acid esters of isothionic acid; and substantially saturated aliphatic acyl amides of saturated monoaminocarboxylic acids having 2 to 6 carbon atoms, and in which the acyl radical contains 12 to 16 carbon atoms, such as sodium-N-lauryl sarcoside. Mixtures of two or more sudsing agents can be used.
A binding material can be added to thicken and provide a desirable consistency to the products of the present invention. Suitable thickening agents include, e.g., water-soluble salts of cellulose ethers, such as, for example, sodium carboxymethyl cellulose, hydroxypropyl cellulose, and hydroxyethyl cellulose. Natural gums such as gum karaya, gum arabic, carrageenan and gum tragacanth, can also be used. Colloidal magnesium aluminum silicate, silica aerogels, silica xerogels, fumed silica, or other finely divided silica can be used as part of the thickening agent for further improved texture. A preferred thickening agent is xanthan gum.
It is also desirable to include some humectant material in toothpaste or gel embodiments of the present invention to keep such products from hardening. Suitable humectants include, e.g., glycerine, sorbitol, polyethylene glycol, propylene glycol, and other edible polyhydric alcohols, as well as mixtures thereof.
Toothpaste or gel products within the scope of this invention may also contain flavoring agents such as, for example, oil of wintergreen, oil of peppermint, oil of spearmint, oil of sassafras, and oil of clove.
Toothpaste or gel products of the present invention may also contain sweetening agents such as, e.g., saccharin, dextrose, levulose, sodium cyclamate, and aspartame. Mixtures of sugar with a sweetener, e.g., sucralose, are also contemplated for use in the present invention.
It is also possible to manufacture the dentifrice products of the present invention in the form of a transparent or translucent gel. This is accomplished by matching the refractive index of the water-humectant system with the abrasives and inorganic thickeners if used.
Professional gels can be formulated similar to dentifrices but with higher fluoride contents. Since these products are not designed for cleaning but only as a fluoride application, abrasives and other cleaning agents need not be included in the formulation.
Other products within the scope of this invention include mouthwashes and rinses. Mouthwashes and rinses generally contain an aqueous solution of ethyl alcohol and flavoring materials. The alcohol provides an antibacterial effect, solubilizes the flavoring materials and provides a pleasant mouth feeling. Alcohol-free mouthwashes are now, however, gaining in popularity. Optionally, mouthwashes and rinses also contain additional antibacterial agents and humectants such as glycerine and sorbitol which give a moist feeling to the mouth.
In addition to the anionic and cationic active ingredients discussed previously herein, mouthwashes and rinses preferably contain from about 0 to about 30%, preferably from about 0 to about 20%, by weight of ethyl alcohol; from about 30% to about 90% by weight of water; from about 0 to about 20% by weight of glycerine or other humectant; from about 0 to about 0.1% by weight of an antibacterial agent; from about 0 to about 0.2% by weight of a soluble fluoride source; from about 0.01% to about 0.5% by weight of a sweetening agent; from about 0.01% to about 2.0% by weight of a flavoring agent; and from about 0.1% to about 1% by weight of an emulsifier-surfactant.
The present invention further provides a two-part packaged product composed of:
(i) a first discrete part containing the aforementioned cationic component in liquid form;
(ii) a second discrete part containing the aforementioned anionic component in liquid form;
(iii) a dispensing container containing a first discrete compartment and a second discrete compartment each with an outlet end, wherein the first compartment stores the first discrete part and the second compartment stores the second discrete part;
(iv) a closure mechanism for closing the first compartment and the second compartment; and
(v) a dispensing means for simultaneously dispensing the liquid cationic component and the liquid anionic component from the product.
A plurality of packaging methods may be employed in order to separately contain or store the two components and provide effective dispensing thereof into the oral cavity.
Thus, the two components of a toothpaste, gel, cream, or the like, may be simultaneously dispensed from separate collapsible tubes preferably made of plastic, a plastic and metal laminate, etc. For convenience and in order to aid in dispensing substantially equal amounts of the components, the tubes may be held together by banding or cementing, preferably along the corresponding ventral sides of the tubes.
In another embodiment, the two tubes may be constructed to have abutting, preferably flat, sidewall portions. In the foregoing embodiments, the mouths of the tubes are usually sufficiently close so that sufficient quantities of the components of the toothpaste or gel may be simultaneously dispensed directly on the toothbrush with the tubes being capped separately.
Alternatively, another packaging method involves loading each component of the paste or gel into separate compartments of the same collapsible composite tube, joined by a common orifice. Such composite tube has compartments separated by a divider which is firmly attached along substantially diametrically opposed portions of the sidewall, and corresponding portions of the head structure of the tube. The divider may be glued or welded to the sidewall and head structure of the tube during manufacture of the latter. The divider is preferably provided with a protruding portion which extends into the mouth of the tube until its edge is substantially flush with the rim of the mouth. Thus, a divider forms with the sidewall two separate compartments of substantially the same volume for storage of the cationic and anionic components, respectively.
In another alternative packaging method, the two tubes are xe2x80x9cconcentricxe2x80x9d. An inner tube lies within and parallel with an outer tube. The mouths of the tubes abut at the same point. Protrusions or the like are inserted between the inner and outer tubes so that the component contained in the outer tube can pass through an available space between the mouth of the outer tube and the mouth of the inner tube. The closures of this tube-within-a-tube (which can screw on the outer tube or simply be held by pressure} may, but does not have to be, equipped with an interior protrusion to fit in the inner tube in order to prevent premature intermixing of the two components at the mouth of the tube.
The tubes of all the above embodiments are usually filled from the bottom and are subsequently sealed together by conventional techniques.
Another alternative packaging arrangement is a pressurized container which is provided with two compartments and two spouts. The internal pressure of the compartments is maintained by a pressurized gas, i.e., nitrogen, at the bottom of each compartment. Operation of a mechanical actuator actuates valves which release the contents of the compartments through the spouts, causing discharge of the paste or gel components onto a brush.
The mouthwash, rinse or similar liquid embodiments are maintained in a manner similar to the pastes or gels in that, during storage, each of the components are maintained separate from one another to prevent premature reaction. Upon dispensing, the components mix and react in the oral cavity to effect remineralization of dental enamel. The liquid components can therefore be stored each in separate compartments of a dual-compartment dispenser. The dispenser usually includes a closure system containing, for example, an inclined crown portion, at least two pouring spouts extending upwardly from an upper surface of the crown portion, and a cover for securement to the crown portion. The cover is provided with closure means, for example, depending plugs, to close the closure. Each pouring spout is preferably provided with a vent opening in addition to product orifices in the spouts. The orifices can be positioned close together on the crown, all of which assists in achieving control over pouring. Transparent containers have proven to be the most satisfactory. Transparency aids a person""s ability to accurately and controllably dispense relatively equal volumes from a dual-compartment dispenser. Transparent walled containers also serve a window function for gauging the amounts of liquid remaining in the dispenser. The walls of the containers can be scribed or otherwise calibrated to assist in dispensing the correct remineralizing amount of the mixed aqueous composition.